tbuckley/cabot-search huggingface dataset:
Circadian Timekeeping in Health and Disease
Authors: Martin C. Moore-Ede, Charles A. Czeisler, Gary S. Richardson
Journal: New England Journal of Medicine (1983)

THE study of circadian (approximately 24-hour) rhythms has within the past decade evolved from a biologic curiosity to a science with enormous implications for clinical medicine. The concurrent maturation of circadian oscillator theory, the anatomic definition of circadian pacemakers in mammals, and the identification of a considerable number of persons with malfunctions of the circadian timing system have formed the basis of a new medical discipline.1 Circadian rhythms relate to clinical medicine in two major ways. First, circadian rhythmicity is such a pervasive element of human physiology that its recognition has required a reassessment of many clinical diagnostic and therapeutic . . .
Neurodegenerative Tauopathies
Authors: Virginia M-Y Lee, Michel Goedert, John Q Trojanowski
Journal: Annual Review of Neuroscience (2001)

▪ Abstract The defining neuropathological characteristics of Alzheimer's disease are abundant filamentous tau lesions and deposits of fibrillar amyloid β peptides. Prominent filamentous tau inclusions and brain degeneration in the absence of β-amyloid deposits are also hallmarks of neurodegenerative tauopathies exemplified by sporadic corticobasal degeneration, progressive supranuclear palsy, and Pick's disease, as well as by hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Because multiple tau gene mutations are pathogenic for FTDP-17 and tau polymorphisms appear to be genetic risk factors for sporadic progressive supranuclear palsy and corticobasal degeneration, tau abnormalities are linked directly to the etiology and pathogenesis of neurodegenerative disease. Indeed, emerging data support the hypothesis that different tau gene mutations are pathogenic because they impair tau functions, promote tau fibrillization, or perturb tau gene splicing, thereby leading to formation of biochemically and structurally distinct aggregates of tau. Nonetheless, different members of the same kindred often exhibit diverse FTDP-17 syndromes, which suggests that additional genetic or epigenetic factors influence the phenotypic manifestations of neurodegenerative tauopathies. Although these and other hypothetical mechanisms of neurodegenerative tauopathies remain to be tested and validated, transgenic models are increasingly available for this purpose, and they will accelerate discovery of more effective therapies for neurodegenerative tauopathies and related disorders, including Alzheimer's disease.
Hypoxia-Inducible Factor-1-Dependent Repression of <i>E-cadherin</i> in von Hippel-Lindau Tumor Suppressor–Null Renal Cell Carcinoma Mediated by TCF3, ZFHX1A, and ZFHX1B
Authors: Balaji Krishnamachary, David Zagzag, Hideko Nagasawa, Karin Rainey, Hiroaki Okuyama, Jin H. Baek, Gregg L. Semenza
Journal: Cancer Research (2006)

Abstract A critical event in the pathogenesis of invasive and metastatic cancer is E-cadherin loss of function. Renal clear cell carcinoma (RCC) is characterized by loss of function of the von Hippel-Lindau tumor suppressor (VHL), which negatively regulates hypoxia-inducible factor-1 (HIF-1). Loss of E-cadherin expression and decreased cell-cell adhesion in VHL-null RCC4 cells were corrected by enforced expression of VHL, a dominant-negative HIF-1α mutant, or a short hairpin RNA directed against HIF-1α. In human RCC biopsies, expression of E-cadherin and HIF-1α was mutually exclusive. The expression of mRNAs encoding TCF3, ZFHX1A, and ZFHX1B, which repress E-cadherin gene transcription, was increased in VHL-null RCC4 cells in a HIF-1–dependent manner. Thus, HIF-1 contributes to the epithelial-mesenchymal transition in VHL-null RCC by indirect repression of E-cadherin. (Cancer Res 2006; 66(5): 2725-31)
High-Altitude Medicine
Authors: John B. West
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Section:ChooseTop of pageAbstract <<Barometric Pressure and A...Physiological Responses t...Genetic Changes at High A...High-Altitude Diseases of...High-Altitude Diseases of...Mitigation of High-Altitu...Commercial and Military A...ReferencesCITING ARTICLES
Bacteria‐Targeted Combined with Photothermal/NO Nanoparticles for the Treatment and Diagnosis of MRSA Infection In Vivo
Authors: Kai Lv, Guowei Li, Xiangjun Pan, Luxuan Liu, Ziheng Chen, Yu Zhang, Hao Xu, Dong Ma
Journal: Advanced Healthcare Materials (2023)

Currently, undeveloped diagnosis and delayed treatment of bacteria-infected sites in vivo not only expand the risk of tissue infection but are also a major clinical cause of multiple drug-resistant bacterial infections. Herein, an efficient nanoplatform for near-infrared (NIR)-light-controlled release and bacteria-targeted delivery of nitric oxide (NO) combined with photothermal therapy (PTT) is presented. Using maltotriose-decorated mesoporous polydopamine (MPDA-Mal) and BNN6, a smart antibacterial (B@MPDA-Mal) is developed to combine bacterial targeting, gas-controlled release, and PTT. Utilizing bacteria's unique maltodextrin transport system, B@MPDA-Mal can accurately distinguish bacterial infection from sterile inflammation and target the bacteria-infected sites for efficient drug enrichment. Moreover, NIR-light causes MPDA to generate heat, which not only effectively induces BNN6 to produce NO, but also raises the temperature to harm the bacteria further. NO/photothermal combination therapy effectively eliminates biofilm and drug-resistant bacteria. The myositis model of methicillin-resistant Staphylococcus aureus infection is established and indicates that B@MPDA-Mal can successfully eradicate inflammation and abscesses in mice. Meanwhile, magnetic resonance imaging technology is used to monitor the treatment procedure and healing outcomes. Given the aforementioned advantages, the smart antibacterial nanoplatform B@MPDA-Mal can be used as a potential therapeutic tool in the biomedical field against drug-resistant bacterial infections.
119P Prospective trial of immuno-(chemo)therapy (IO) prior to resection, definitive chemo-radiotherapy, or palliative therapy in patients with borderline resectable non-small cell lung cancer (NSCLC) including oligometastatic disease (KOMPASSneo)
Authors: M. Faehling, K. Lehrach, S. Fallscheer, B. Schwenk, S. Kramberg, J. Sträter, S. Eschmann, M. Hetzel, F. Heinzelmann, R. Sätzler
Journal: Journal of Thoracic Oncology (2023)
Safety and Efficacy of Axicabtagene Ciloleucel versus Standard of Care in Patients 65 Years of Age or Older with Relapsed/Refractory Large B-Cell Lymphoma
Authors: Jason R. Westin, Frederick L. Locke, Michael Dickinson, Armin Ghobadi, Mahmoud Elsawy, Tom van Meerten, David B. Miklos, Matthew L. Ulrickson, Miguel-Angel Perales, Umar Farooq, Luciano Wannesson, Lori Leslie, Marie José Kersten, Caron A. Jacobson, John M. Pagel, Gerald Wulf, Patrick Johnston, Aaron P. Rapoport, Linqiu Du, Saran Vardhanabhuti, Simone Filosto, Jina Shah, Julia T. Snider, Paul Cheng, Christina To, Olalekan O. Oluwole, Anna Sureda
Journal: Clinical Cancer Research (2023)

Older patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) may be considered ineligible for curative-intent therapy including high-dose chemotherapy with autologous stem-cell transplantation (HDT-ASCT). Here, we report outcomes of a preplanned subgroup analysis of patients ≥65 years in ZUMA-7.
Ensuring Public Trust in an Empowered FDA
Authors: Joseph S. Ross, Karina M. Berg, Reshma Ramachandran
Journal: New England Journal of Medicine (2023)

Interview with Dr. Joseph Ross on shifts in the FDA's use of accelerated approval and associated challenges for clinicians and patients. (12:17)Download The FDA's recent approval of lecanemab for Alzheimer's disease has been clouded by controversy over other accelerated approvals, illustrating challenges faced by the agency.
Thermophobic Trehalose Glycopolymers as Smart C‐Type Lectin Receptor Vaccine Adjuvants
Authors: Aaron T. Hendricksen, Shahrzad Ezzatpour, Anunay J. Pulukuri, Austin T. Ryan, Tatum J. Flanagan, William Frantz, David W. Buchholz, Victoria Ortega, Isaac A. Monreal, Julie M. Sahler, Amy E. Nielsen, Hector C. Aguilar, Rock J. Mancini
Journal: Advanced Healthcare Materials (2023)

Herein, this work reports the first synthetic vaccine adjuvants that attenuate potency in response to small, 1-2 °C changes in temperature about their lower critical solution temperature (LCST). Adjuvant additives significantly increase vaccine efficacy. However, adjuvants also cause inflammatory side effects, such as pyrexia, which currently limits their use. To address this, a thermophobic vaccine adjuvant engineered to attenuate potency at temperatures correlating to pyrexia is created. Thermophobic adjuvants are synthesized by combining a rationally designed trehalose glycolipid vaccine adjuvant with thermoresponsive poly-N-isoporpylacrylamide (NIPAM) via reversible addition fragmentation chain transfer (RAFT) polymerization. The resulting thermophobic adjuvants exhibit LCSTs near 37 °C, and self-assembled into nanoparticles with temperature-dependent sizes (90-270 nm). Thermophobic adjuvants activate HEK-mMINCLE and other innate immune cell lines as well as primary mouse bone marrow derived dendritic cells (BMDCs) and bone marrow derived macrophages (BMDMs). Inflammatory cytokine production is attenuated under conditions mimicking pyrexia (above the LCST) relative to homeostasis (37 °C) or below the LCST. This thermophobic behavior correlated with decreased adjuvant R
Issue Information
Journal: Allergy (2023)

Through the eyes of children About the cover Allergic/Infl ammatory Skin DiseasesThe skin is the largest immune organ that serves as a protec ve layer between the body and the environment.Skin barrier restricts water loss and prevents the entry of external poten ally harmful substances.Once the integrity of the barrier is compromised by environmental pollutants and parasites, the produc on of alarmins ini ates type 2 immune responses.The ac va on and skin migra on of infl ammatory cells, such as T cells, dendri c cells and macrophages contribute to the pathogenesis of atopic derma s.Con nued ac va on of these responses maintains the infl ammatory cycle, leading to further infl amma on, itch, and skin barrier disrup on.In this issue, Brough et al., in their editorial, discuss the short-term use of emollients for the preven on of atopic derma s in high-risk infants.Chaoimh and Lad et al. demonstrate that daily emollient use ini ated in the fi rst week of life un l two months signifi cantly reduces the incidence of atopic derma s in the fi rst year of life.In contrast, Bradshaw et al. did not fi nd any benefi cial eff ect of daily emollient use in the fi rst year of life in preven ng or delaying atopic derma s, food allergy, asthma or hay fever.Jeong et al. show the essen al role of Ras-related protein Rab-25 in epidermal diff eren a on by coordina ng keratohyalin granules matura on and assembly, and demonstrate that its defi ciency is correlated with atopic derma s severity.Renert-Yuval, Pavel, and Del Duca et al. provide insights into the eff ects of Th2 modula on with dupilumab on the immune and hair kera n dysregula on in alopecia areata, par cularly in pa ents with an atopic background.
118P High dose chemo-radio-immunotherapy for NSCLC III: ESR/ATS thresholds for DLCO correlate with radiation dosimetry and predict pneumonitis
Authors: F. Zehentmayr, B. Grambozov, J. Karner, E. Ruznic, C. Gaisberger, G. Fastner, B. Zellinger, R. Moosbrugger, M. Studnicka, F. Sedlmayer, M. Stana
Journal: Journal of Thoracic Oncology (2023)
Organ‐specific allergen challenges in airway allergy: Current utilities and future directions
Authors: J. L. Fauquert, C. Alba‐Linero, A. Gherasim, A. Testera‐Montes, G. Bentabol‐Ramos, R. Saenz de Santa Maria‐Garcia, M. J. Torres, I. Eguiluz‐Gracia, C. Rondon
Journal: Allergy (2023)

Atopy has been long used as the screening method for airway allergy. Nevertheless, aeroallergens can trigger respiratory symptoms not only in atopic patients (atopic respiratory allergy, ARA), but also in non-atopic subjects (local respiratory allergy, LRA). Moreover, ARA and LRA can coexist in the same patient, and this clinical scenario has been called dual respiratory allergy (DRA). When the clinical history cannot determine the relevance of sensitizations in ARA patients, nasal, conjunctival or bronchial allergen challenges (NAC, CAC, and BAC, respectively) should be conducted. Moreover, these tests are required to identify patients with LRA and DRA. The clarification of the allergic triggers of airway diseases has a profound impact on the management strategies the patients can be offered. Importantly, allergen immunotherapy (AIT) remains as the only disease-modifying intervention for ARA. Recent data indicate that AIT might have a similar effect on LRA patients. Nevertheless, AIT success relies largely on the correct phenotyping of allergic individuals, and NAC, CAC, and BAC are very helpful tools in this regard. In this review, we will summarize the main indications and methodology of CAC, NAC, and BAC. Importantly, the clinical implementation of these tests might translate into precision medicine approaches and better health outcomes for patients with airway allergy.
Erratum to “Pre-existing Castration-resistant Prostate Cancer–like Cells in Primary Prostate Cancer Promote Resistance to Hormonal Therapy” [Eur Urol 2022;81(5):446–55]
Authors: Qing Cheng, William Butler, Yinglu Zhou, Hong Zhang, Lu Tang, Kathryn Perkinson, Xufeng Chen, Xiaoyin “Sara” Jiang, Shannon J. McCall, Brant A. Inman, Jiaoti Huang
Journal: European Urology (2023)
Implications from COVID-19 for future pandemic global health governance
Authors: Jeffrey V. Lazarus, Cristina Pujol-Martinez, Christopher J. Kopka, Carolina Batista, Wafaa M. El-Sadr, Rocio Saenz, Ayman El-Mohandes
Journal: Clinical Microbiology and Infection (2023)

Limitations of current global health governance revealed during the COVID-19 pandemic can inform the ongoing deliberations of an international treaty on pandemics.
Host and primary tumor factors for the development of multiple cutaneous squamous cell carcinomas among a retrospective cohort in Rhode Island
Authors: Isabelle Moseley, Fadwa Ahmed, Erica Lin, Rachel Lim, Megan Hoang, Navya Baranwal, Leslie Robinson-Bostom, Tiffany Libby, Oliver Wisco, Abrar Qureshi, Eunyoung Cho
Journal: Journal of the American Academy of Dermatology (2023)
Pushing (for) GOLD
Authors: Mark Dransfield, Ravi Kalhan, Daiana Stolz
Journal: European Respiratory Journal (2023)

In this issue of the European Respiratory Journal , Agustí et al. [1] present the Executive Summary of the updated Global Initiative for Chronic Obstructive Lung Disease (GOLD) report for 2023. The updated report includes a number of important changes to the group's recommendations for the diagnosis, assessment and treatment of COPD that have immediate relevance for the practising clinician. The current changes might also represent the most consequential shift in overall strategy since GOLD's inception, and the report follows on the heels of a number of provocative publications suggesting new approaches to the definition and nomenclature of stable COPD [2] and exacerbations [3, 4], as well as a wholesale rethinking of the disease [5]. GOLD 2023: key updates and potential missed opportunities <https://bit.ly/42egTLx>
The effects of elexacaftor/tezacaftor/ivacaftor beyond the epithelium: spurring macrophages to fight infections
Authors: Emanuela M. Bruscia
Journal: European Respiratory Journal (2023)

Elexacaftor/tezacaftor/ivacaftor (ETI) is a modulator therapy recently approved for patients with cystic fibrosis (CF) with at least one F508del mutation. The resulting impact on the health of CF patients has been tremendous, improving many clinical aspects ( e.g. sweat chloride, lung function and reduction in pulmonary exacerbation) of this complex disease, and enhancing patients' quality of life [1]. Elexacaftor/tezacaftor/ivacaftor treatment improves the antimicrobial function of monocytes/macrophages http://bit.ly/3ZvIsxZ
Rapid response of cutaneous lupus erythematosus to treatment with the type 1 interferon receptor antagonist anifrolumab
Authors: Claudia Günther
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof Rapid response of cutaneous lupus erythematosus to treatment with the type 1 interferon receptor antagonist anifrolumab Get access Claudia Günther Claudia Günther Department of Dermatology, University Medical Center Hospital TU Dresden, Dresden, Germany Correspondence: Claudia Günther. Email: claudia.guenther@ukdd.de https://orcid.org/0000-0002-4330-1861 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad111, https://doi.org/10.1093/bjd/ljad111 Published: 01 April 2023 Article history Received: 27 March 2023 Accepted: 29 March 2023 Published: 01 April 2023 Corrected and typeset: 26 May 2023
Hailey–Hailey disease (benign familial pemphigus) responsive to treatment with ocrelizumab for multiple sclerosis
Authors: Sarah R Adamson, Claire L Higgins, Emma  Veysey
Journal: British Journal of Dermatology (2023)

Benign familial pemphigus, also known as Hailey–Hailey disease (HHD), is a rare autosomal-dominant genetic skin disorder characterized by symmetrical, well-demarcated, erythematous, painful erosive and crusted plaques in the intertrigous regions. Treatment options are limited and aimed at control and limiting complications. Ocrelizumab, an anti-CD20 antibody, was given to treat our patient’s multiple sclerosis, and incidentally found to have cleared her HHD, thus offering a potential effective treatment option.
Understanding the real-world patient journey and unmet needs of people with hidradenitis suppurativa through social media research
Authors: Joslyn S Kirby, Antonio Martorell, Christopher J Sayed, Ivette Alarcon, Torben Kasparek, Susan Frade, Barry M McGrath, Bente Villumsen, Christos C Zouboulis
Journal: British Journal of Dermatology (2023)

People with hidradenitis suppurativa (HS) have a high burden of unmet needs and a better understanding of their lived experience is needed. Social media research is a novel approach that can improve such understanding by collecting and analysing publicly available information related to patient experiences. This study found that people with HS are unhappy with the management of their disease and highlights the need for greater awareness and research, as well as treatment effectiveness and options.
Single-cell and spatially resolved transcriptomics for liver biology
Authors: Ping Lin, Xi Yan, Siyu Jing, Yanhong Wu, Yiran Shan, Wenbo Guo, Jin Gu, Yu Li, Haibing Zhang, Hong Li
Journal: Hepatology (2023)

Single-cell transcriptomics enables the identification of rare cell types and the inference of state transitions, whereas spatially resolved transcriptomics allows the quantification of cells and genes in the context of tissues. The recent progress in these new technologies is improving our understanding of the cell landscape and its roles in diseases. Here, we review key biological insights into liver homeostasis, development, regeneration, chronic liver disease, and cancer obtained from single-cell and spatially resolved transcriptomics. We highlight recent progress in the liver cell atlas that characterizes the comprehensive cellular composition; diversity and function; the spatial architecture such as liver zonation, cell communication, and proximity; the cell identity conversion and cell-specific alterations that are associated with liver pathology; and new therapeutic targets. We further discuss outstanding challenges, advanced experimental technologies, and computational methods that help to address these challenges.
Reply to correspondence “Food allergens to emollients”
Authors: Alan D. Irvine, Jonathan O'. B. Hourihane
Journal: Allergy (2023)

ADI is a consultant/on the advisory board for AbbVie, Novartis, Regeneron, Sanofi Genzyme, Pfizer, Eli Lilly, Amgen, Benevolent AI, LEO, Arena. JO'BH receives research funding, speaker fees, and consultancy fees from Aimmune Therapeutics, research funding and speaker fees from DBV Technologies, and research funding from Clemens von Pirquet Foundation and Temple St Hospital Foundation. A patent application has been submitted by Johnson & Johnson based on these results, with JO'BH and ADI named as inventors.
Design considerations and implications of findings on progressive pulmonary fibrosis from the prospective Canadian Registry for Pulmonary Fibrosis
Authors: Christopher J. Ryerson, Nathan Hambly, Martin Kolb
Journal: European Respiratory Journal (2023)

We thank O. Moran-Mendoza and co-workers for their interest in our recent publication on the prevalence of progressive pulmonary fibrosis (PPF) within the Canadian Registry for Pulmonary Fibrosis (CARE-PF) [1]. The authors have raised several important points, which we have summarised and addressed as follows. Readers should be aware of both the advantages and limitations of data drawn from prospective registries. <https://bit.ly/40V3TK7>
What could explain the high prevalence of progressive fibrosing interstitial lung disease in a patient registry?
Authors: Onofre Moran-Mendoza, Ahmad Al-Jarallah, Salem Alqahtani, Carla Paredes
Journal: European Respiratory Journal (2023)

<b>It is important to standardise diagnostic protocols and data collection processes across centres participating in registries, to avoid or reduce the risk of diagnostic misclassification bias and other related types of biases in registry-based studies</b>http://bit.ly/3D7lvIA
Facial involvement is reflective of patients’ global perception of vitiligo extent
Authors: Samar Merhi, Pascale Salameh, Mounya Abboud, Julien Seneschal, Viktoria  Eleftheriadou, Isabelle Pane, Viet-Thi Tran, Jason Shourick, Khaled  Ezzedine
Journal: British Journal of Dermatology (2023)

Abstract Background The involvement of visible areas in vitiligo has been found to be correlated with increased psychiatric morbidity. Although multiple tools have been developed to assess vitiligo, no cutoff for improvement or worsening of vitiligo from a patient’s perspective has been established. Objectives To determine the minimal clinically important difference (MCID) of the Self-Assessment Vitiligo Extent Score (SA-VES) in patients with vitiligo and to evaluate, from the patient’s perspective, the importance of the change in the involvement of visible areas (face and hands) in patients’ overall perception of disease worsening or improving. Methods This was a cross-sectional study in the context of the ComPaRe e-cohort. Adult patients with vitiligo were invited to answer online questionnaires. They completed the SA-VES twice, 1 year apart. In addition, patients answered a 5-point Likert anchor question aimed at assessing their perception of the evolution of the extent of their vitiligo. The MCID was calculated using distribution- and anchor-based approaches. Using ordinal logistic regression, the change of vitiliginous lesions on the face or hands was compared to the overall extent of vitiligo (patches on all body areas). Results In total, 244 patients with vitiligo were included in the analyses; 20 (8%) were found to have an improvement in their vitiligo. The MCID in worsened patients was equal to a 1.3% body surface area [95% confidence interval (CI) 1.01–1.43] increase in the SA-VES. For participants with improved vitiligo, the MCID was equal to a decrease in total SA-VES of 1.3% (95% CI 0.867–1.697). Patients’ perceptions of change in their vitiligo was increased sevenfold when it affected the face vs. the rest of the body. Conclusions Changes in the facial SA-VES were highly correlated with patients’ impressions of the extent of vitiligo.
Strain estimation in aortic roots from 4D echocardiographic images using medial modeling and deformable registration
Authors: Ankush Aggarwal, Peter Mortensen, Jilei Hao, Łukasz Kaczmarczyk, Albert T. Cheung, Lourdes Al Ghofaily, Robert C. Gorman, Nimesh D. Desai, Joseph E. Bavaria, Alison M. Pouch
Journal: Medical Image Analysis (2023)